NRK-52E

FAIK3-5 Cells Die Mostly by Necrosis at High Cd Concentrations Whereas NRK-52E Cells Die by Apoptosis at All Cd Concentrations Tested

Cadmium (Cd) disrupts renal hypoxia-PHD-HIFα (HPH) signaling and promotes chronic kidney disease (CKD), yet its molecular impact on renal cells remains unclear. Schreiber et al. examined how Cd interferes with HPH signaling in two kidney-derived cell lines and tests whether hypoxic preconditioning can mitigate Cd toxicity. Using NRK-52E proximal-tubule and FAIK3-5 EPO-producing renal cells, they exposed them to Cd²⁺ (2.5-20 µM) under chemical (DMOG) or hypoxic (1% O₂) HPH activation.

To determine Cd toxicity, both apoptosis and necrosis were investigated. Apoptosis was measured by immunoblotting for PARP-1 cleavage and quantifying the ratio of cleaved PARP-1 over total PARP-1, while necrosis was measured by quantifying trypan blue uptake. As shown in Figure 1, after 24 h of Cd exposure, the cell lines behaved differently. FAIK3-5 cells were insensitive to <5 µM Cd, died mainly by necrosis at 15-20 µM Cd (~60%), and ~30% died by apoptosis at 10-20 µM Cd. In contrast, NRK-52E cells showed increased apoptosis (about 30%) at 2.5-5 µM Cd, which remained elevated (~40%) up to the highest Cd concentration tested, consistent with previous studies. Trypan blue uptake was elevated at 20 µM Cd but was still ~100-fold lower than in FAIK3-5 cells, also reflected by more live NRK-52E cells at 20 µM Cd. In summary, both cell lines are sensitive to Cd, but FAIK3-5 cells mainly die by necrosis at high Cd concentrations, while NRK-52E cells largely die by apoptosis at all tested Cd concentrations.